The anti-proliferative and anti-angiogenic activity of a few compounds structurally related to the class of the compounds described in the present invention has been reported.
(6-[3′-(1-adamantyl)-4′-hydroxyphenyl]-2-naphthalenecarboxylic acid (AHPN) also named CD437) (Cancer Research, 2002; 62(8), 2430-6; Blood, 2000; 95, 2672-82; Leukemia, 1999, 13, 739-49; Cancer Letters, 1999, 137, 217-2) is reported to be selective for the retinoic acid receptor-gamma RAR-γ, to inhibit cell growth and induces apoptosis in breast carcinoma, melanoma and cervical carcinoma cell lines, including those all trans-retinoic acid- (ATRA-) resistant, with a mechanism independent of receptor binding (WO9703682; J. Med. Chem. 1995, 38, 4993-5006).
In addition, some compounds related to this class of compounds, such as TAC-101 (Clin. Cancer Res. 1999, 5, 2304-10) or derivatives such as RE-80, AM-580 or Am-80 (Eur. J. Pharmacol. 1993, 249, 113-6) have shown antiangiogenic properties.
Novel compounds, which are biphenyl derivatives of acrylic acid have recently been described (Cincinelli R. et al., J. Med. Chem. 2003, 46: 909-912 and WO03/11808). In particular, compound named ST1926 (E-3-(4′-hydroxy-3′-adamantylbiphenyl-4-yl)acrylic acid) was shown to have a potent antiproliferative activity on a large panel of human tumour cells.
One of the last developed analogue of CD437, compound (E)-4-[3′-(1-adamantyl)-4′-hydroxyphenyl]-3-chlorocinnamic acid (3-Cl-AHPC) (Dawson, M. I. et al. J. Med. Chem. 2004, 47(14), 3518-3536; WO0348101) is reported to inhibit the proliferation and to induce apoptosis of cancer cells both in vitro and in vivo.
Patent JP10182583 discloses some phenylcinnamohydroxamic acid derivatives having a differentiating-inducing action on cancer cells and useful as a medicines for treatment of malignant tumours, autoimmune diseases and skin diseases.